The precise ontogenetic range of human lymphocytes susceptible to transformation by Epstein-Barr Virus (EBV) has not been defined. Recent but incomplete evidence suggests that EBV may transform a range of B-lymphocyte phenotypes, from "early" (non-Ig producing) B-cells through pre-B cells and B-cells. Analyses of Ig expression and cytogenetic phenomena in Burkitt tumor cells suggest that the oncogenic event which distinguishes them from other EBV-transformed cells may be associated with a particular stage in their Ig-gene differentiation program. This oncogenic event may include a human c-myc gene translocation. We will attempt to better define the ontogenetic range of human lymphocytes susceptible to EBV-mediated transformation. Primary mononuclear cells from human fetal, neonatal, and adult tissues will be clonally transformed in agarose medium. Clonally propagated lines will then be phenotyped by analysis of Ig expression, surface "Ia" antigen, and other surface epitopes. Karyotype analyses will also be done. The cell clones will then be analyzed for their patterns of Ig gene rearrangements. Cell clones with aberrant rearrangements of non-expressed Ig gene alleles will be examined for evidence of rearrangement of the cellular c-myc gene, or chromosomal translocation. The results of our studies should yield a clearer picture of the stages of human (B-) lymphocyte ontogeny which are susceptible to transformation by EBV. We may be able to partially illuminate how clinically malignant B-cell clones emerge from a polyclonally transformed population.